To endure in hosts through their ability to establish a life-long persistent infection often associated with pathogenesis, ?-2 herpesviruses effectively antagonize host immune responses through various mechanisms. The goal of this study is to better understand how ?-2 herpesviruses evade host PCD-mediated innate immunity, with a specific focus on the viral FLICE-like inhibitor protein (FLIP), designated as vFLIP. The main hypothesis of this grant is: a novel viral immune evasion and pathogenic strategy wherein vFLIP targets NF-?B, apoptosis, and autophagy to escape host PCD-mediated innate immunity and tumor suppression, ultimately contributing to the persistence and/or pathogenesis of ?-2 herpesviruses.